Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study

Abstract

The mechanism of the observed association between body mass, particularly centralized body fat, and postmenopausal breast cancer risk is not well understood. We hypothesized that body mass may affect DNA methylation through increased estrogen and chronic inflammation. The association between body mass and promoter methylation in breast tumors was investigated in a population-based, case-control study. The promoter methylation of E-cadherin, p16, and RAR-β(2) genes was assessed in breast tumor blocks from 803 pre- and postmenopausal cases by using real-time methylation-specific polymerase chain reaction. Unconditional logistic regression was used to derive the adjusted OR and 95% CI for case-case comparisons of tumors with and without promoter methylation of the genes. The frequency of promoter methylation was 20% for E-cadherin, 25.9% for p16, and 27.5% for RAR-β(2). There was no difference in the prevalence of the DNA methylation of individual genes by BMI, waist-to-hip ratio (WHR), or lifetime weight change between the age of 20 y and the present. However, in a case-case comparison of postmenopausal breast cancer, a greater WHR was associated with an increased likelihood of ≥1 of the 3 genes being methylated (OR: 1.85; 95% CI: 1.10, 3.11; P-trend < 0.02). We showed that WHR was associated with DNA promoter methylation of ≥1 of 3 genes in postmenopausal breast tumors. It may be that the association of body fat composition and postmenopausal breast cancer is related to altered DNA methylation. However, future studies in other populations and with an examination of the methylation of more genes are needed.